Advancing age is accompanied by profound changes in autonomic nervous syste activity, both at rest and during exercise as well as reduction in the cardiovascular response to autonomic stimulation. We have undertaken three separate but conceptually interrelated studies to quantify the relationship between aging and autonomic modulation of cardiovascular performance. A. Efferent muscle sympathetic nerve activity (MSNA) recording from the peroneal nerve will be performed in the Baltimore Longitudinal Study of Aging (BLSA) men and women across a broad age range at rest and in response to baroreflex stimulation and static exercise. We hypothesize that in addition to age, other factors such as gender, aerobic fitness and body composition will modulate the MSNA response to these stimuli. B. To ascertain the importance of the beta-adrenergic system on age-associated changes in hemodynamics during aerobic exercise (EX), we performed maximal cycle EX in 25 healthy men ages 28-72 yr from the BLSA after acute beta- blockade with intravenous propranolol. In these men,end-diastolic volume index (EDVI) at peak workload declined with age (r= - 0.45) causing an age- associated decline in stroke volume index (SVI) (r= 0.48, p<0.05) not present in 70 unblocked men. The decline in heart rate (HR) with age in propranolol-treated men was blunted (0.46 beats/min/yr) compared to control (1.09 beats/min/yr). The primary reason for the slope shifts in the age regressions after propranolol was a large increase in EDVI and SVI and a large decrease in HR in younger men. Similarly, intravenous propranolol resulted in reduced peak filling rates with EX in young (27 q 8 yr) but not older (62 q 6 yr) men relative to their unmedicated age peers. We conclude that age differences in beta-adrenergic responsiveness underlie many of the age-associated changes in hemodynamics during vigorous aerobic EX. C. To determine the role of the autonomic nervous system on age-associated differences in aerobic capacity and plasma catecholamines, we performed acute autonomic blockade with intravenous propranolol (0.15 mg/kg) and atropine (0.025 mg/kg) in 10 young (<40 yr old) and 10 older (>60 yr old) healthy BLSA volunteers prior to maximal treadmill exercise, in a placebo- controlled crossover trial. Plasma catecholamines were monitored before, during and immediately following exercise. Statistical analysis will determine whether age per se differentially modifies the effect of autonomi blockade on VO2max, HR and blood pressure response and plasma catecholamine during maximal exercise.